This project is a continuation of an investigation into regulation of intermediary metabolism in the kidney by acid-base changes and the relationship of such regulation to physiologic processes involved in acid-base hemeostasis. In previous studies we have related two physiologic processes, the chronic increase in NH4 ion excretion and glutamine utilization in metabolic acidosis and the acute increase in citrate clearance in metabolic alkalosis, to chronic and acute effects of acid-base changes on glutamine and citrate metabolism by tissue slices and mitochondria from renal cortex. Specifically these physiologic changes have been shown to be related to alterations in the rate of transport of citrate and glutamine across the inner mitochondrial membrane. Recently we have developed a general hypothesis, which emphasizes the regulatory role of mitochondrial substrate carriers, to account for the major known acute and chronic effects of acid-base changes on renal metabolism. In the proposed research further evidence for this hypothesis will be sought. Acute effects will be examined by metabolic studies of intact kidneys, tissue slices and isolated mitochondria from dog, rabbit and rat. Tissue from chronically acidotic and alkalotic litter mate dogs will be used to examine chronic effects on transport and metabolism of various substrates.